This proposal is to request support for a Keystone Symposia meeting entitled "Towards Identifying the Pathophysiology of Autistic Syndromes", organized by Joseph Piven and Pat Levitt, which will be held in Santa Fe, New Mexico from February 24 - 28, 2008. Autism is a common and highly heritable, neurodevelopmental disorder defined by the co-occurrence of three characteristic, behavioral features: deficits in social interactions, abnormalities in verbal and non-verbal communication and highly restricted interests and repetitive behaviors. The developmental etiology and specific pathogenetic mechanisms underlying autism are unknown, but the pathophysiology that underlies a small subset of etiologically-defined, rarer neuro-developmental disorders, thought to be associated with autism and autistic behaviors -e.g., Fragile X Syndrome, tuberous sclerosis, Smith-Lemli-Opitz Syndrome and Rett Syndrome-have been well-described. Yet there is disproportionately little research on these conditions as models for understanding autism. Accumulating data suggest that an underlying pathophysiology in the development of brain connectivity (Zoghbi 2003) may be the point of convergence across all of these disorders. This conference brings together a unique group of clinical and basic scientists to examine what is known about the genetic and neurobiological underpinnings of this subset of disorders as a starting point for identifying the pathophysiological basis of autism. Autism is a severe neurodevelopmental disorder affecting an estimated 1/150 school-aged children (Charles 2007) constituting a major public health problem. Despite the often extraordinary time and expense committed to their education and care, autistic individuals rarely achieve normal social and communicative functioning, and most require supervision throughout their lives, resulting in a substantial burden to affected individuals, their families and communities. [unreadable] [unreadable] [unreadable]